Substantial evidence exists indicating that CNS-epinephrine (Epi) plays an important role in the regulation of behavior, neuroendocrine function and cardiovascular function. Recent data from neurotoxin studies and from immunocytochemical studies suggests that the biosynthetic enzyme phenylethanolamine-N-methyltransferase (PNMT) and Epi may not coexist in the same neurons in the hypothalamus. These data contradict the generally accepted concepts concerning the disposition and biosynthesis of CNS Epi. Preliminary evidence has been generated in our laboratory to suggest that epinine may serve as an intermediate in the biosynthesis of Epi, thus, explaining the neurotoxin and immunocytochemical data recently reported. Therefore the primary objective of this project will be to further elucidate the epinine-mediated biosynthetic pathway to Epi in rat hypothalamus and to determine whether epinine is simply a biosynthetic intermediate or whether it is stored and released from NPMT-containing neurons in the hypothalamus. Information generated from this study will allow for a more rational approach to the design of drugs capable of specifically altering CNS Epi levels.